Abstract

In this talk, we shall see why biomolecular structure determination and deciphering the dynamics assigned to a given 3D structure is important. Then, we shall differentiate chemical shifts from “shifted chemicals” and move on to the description of a new method to determine and validate protein structure and dynamics via a hybrid theory-experiment approach. Do not read the rest!

In contrasts to the ever-growing use of the NMR observables that stem from protein backbone atoms, there have been a few studies on the structure – NMR chemical shift interconnection for the protein amino acid residue side-chains. Proteins are rich of side-chain methyls and conjugated rings, many of which, owing to their hydrophobic nature, are more frequently placed at the inner core and protein-protein interfaces. Thus, naturally incorporated in proteins, those side-chains are excellent probes of biomolecular structure, dynamics and recognition. This work targets the development and exploitation of the structure-based predictors of methylic and aromatic side-chain chemical shifts by incorporating the terms that are intrinsically convenient for the introduction of restraining forces in future molecular dynamics simulations. The predictors are tested for their usefulness in validation of protein structures and dynamical ensembles, as well as in scoring different protein docking proposals. The web server and stand-alone programme implementations are created to facilitate the usage of the developed tools. Their performance is demonstrated to already provide an excellent opportunity for their immediate implementation in restrained simulations to refine protein structure and dynamics from the side-chain perspective.